التفاصيل البيبلوغرافية
| العنوان: |
EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion |
| المؤلفون: |
Chotirat Rattanasinchai, Kathleen A. Gallo, Jann N. Sarkaria, Ashley Sample, Jian Chen, Sean A. Misek, Laura E. Schroeder |
| المصدر: |
Molecular cancer research : MCR. 15(8) |
| سنة النشر: |
2016 |
| مصطلحات موضوعية: |
0301 basic medicine, MAPK/ERK pathway, rac1 GTP-Binding Protein, Cancer Research, MAP Kinase Kinase 4, Cell, RAC1, Biology, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Cell Line, Tumor, medicine, Humans, Neoplasm Invasiveness, Protein kinase A, Molecular Biology, MAP kinase kinase kinase, Kinase, Cell migration, MAP Kinase Kinase Kinases, rac GTP-Binding Proteins, ErbB Receptors, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, Guanine nucleotide exchange factor, Neoplasm Recurrence, Local, Glioblastoma, Signal Transduction |
| الوصف: |
A hallmark of glioblastoma (GBM) tumors is their highly invasive behavior. Tumor dissemination into surrounding brain tissue is responsible for incomplete surgical resection, and subsequent tumor recurrence. Identification of targets that control GBM cell dissemination is critical for developing effective therapies to treat GBM. A majority of GBM tumors have dysregulated EGFR signaling, due most frequently to EGFR amplification or the presence of a constitutively active EGFRvIII mutant. Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that can activate multiple MAPK pathways. In this study, evidence is provided that MLK3 is essential for GBM cell migration and invasion, and that an MLK inhibitor blocks EGF-induced migration and invasion. MLK3 silencing or MLK inhibition blocks EGF-induced JNK activation, suggesting that MLK3-JNK signaling promotes invasion of GBM cells. Mechanistically, it is demonstrated that DOCK180, a RAC1 guanine nucleotide exchange factor (GEF) overexpressed in invasive GBM cells, activates the MLK3-JNK signaling axis in a RAC1-dependent manner. In summary, this investigation identifies an EGFR–DOCK180–RAC1–MLK3–JNK signaling axis that drives glioblastoma cell migration and dissemination. Implications: On the basis of these findings, MLK3 emerges as a potential therapeutic target for the treatment of glioblastoma. Mol Cancer Res; 15(8); 1085–95. ©2017 AACR. |
| تدمد: |
1557-3125 |
| الوصول الحر: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ad096409303ad23de9c06f47c1775d7Test
https://pubmed.ncbi.nlm.nih.gov/28487380Test |
| حقوق: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....9ad096409303ad23de9c06f47c1775d7 |
| قاعدة البيانات: |
OpenAIRE |
